ArticleDiabetologia2008
Glucose increases hepatic lipase expression in HepG2 liver cells through upregulation of upstream stimulatory factors 1 and 2.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- The impact of dietary interventions on cardiometabolic health.Cardiovascular diabetology · 2025Review
- Sex-specific responses in glucose-insulin homeostasis and lipoprotein-lipid components after high-dose supplementation with marine n-3 PUFAs in abdominal obesity: a randomized double-blind crossover study.Frontiers in nutrition · 2023Article
- Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.Frontiers in endocrinology · 2022Article
- Evolutionary genetics and acclimatization in nephrology.Nature reviews. Nephrology · 2021Review
- Fetal High-Density Lipoproteins: Current Knowledge on Particle Metabolism, Composition and Function in Health and Disease.Biomedicines · 2021Review
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- Differential Impact of Flavonoids on Redox Modulation, Bioenergetics, and Cell Signaling in Normal and Tumor Cells: A Comprehensive Review.Antioxidants & redox signaling · 2018Review
- The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk.Lipids in health and disease · 2017Review
- Significant association between upstream transcription factor 1 rs2516839 polymorphism and hepatocellular carcinoma risk: a case-control study.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Requirement of the transcription factor USF1 in bovine oocyte and early embryonic development.Reproduction (Cambridge, England) · 2015Article
- Premature aging of leukocyte DNA methylation is associated with type 2 diabetes prevalence.Clinical epigenetics · 2015Article
- Apoptotic events induced by high glucose in human hepatoma HepG2 cells involve endoplasmic reticulum stress and MAPK's activation.Molecular and cellular biochemistry · 2015Article
- Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines.BioMed research international · 2015Article
- Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholesterolemia.Epigenetics · 2014Article
- Multiple E-boxes in the distal promoter of the rat pyruvate carboxylase gene function as a glucose-responsive element.PloS one · 2014Article
- Upstream stimulatory factors 1 and 2 mediate the transcription of angiotensin II binding and inhibitory protein.The Journal of biological chemistry · 2013Article
- HDL dysfunction in diabetes: causes and possible treatments.Expert review of cardiovascular therapy · 2012Review
- Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood.Human molecular genetics · 2012Article
- n-3 PUFA as regulators of cardiac gene transcription: a new link between PPAR activation and fatty acid composition.Lipids · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisElevated hepatic lipase (HL, also known as LIPC) expression is a key factor in the development of the atherogenic lipid profile in type 2 diabetes and insulin resistance. Recently, genetic screens revealed a possible association of type 2 diabetes and familial combined hyperlipidaemia with the USF1 gene. Therefore, we investigated the role of upstream stimulatory factors (USFs) in the regulation of HL.
methodsLevels of USF1, USF2 and HL were measured in HepG2 cells cultured in normal- or high-glucose medium (4.5 and 22.5 mmol/l, respectively) and in livers of streptozotocin-treated rats.
resultsNuclear extracts of cells cultured in high glucose contained 2.5 +/- 0.5-fold more USF1 and 1.4 +/- 0.2-fold more USF2 protein than cells cultured in normal glucose (mean +/- SD, n = 3). This coincided with higher DNA binding of nuclear proteins to the USF consensus DNA binding site. Secretion of HL (2.9 +/- 0.5-fold), abundance of HL mRNA (1.5 +/- 0.2-fold) and HL (-685/+13) promoter activity (1.8 +/- 0.3-fold) increased in parallel. In chromatin immunoprecipitation assays, the proximal HL promoter region was immunoprecipitated with anti-USF1 and anti-USF2 antibodies. Co-transfection with USF1 or USF2 cDNA stimulated HL promoter activity 6- to 16-fold. USF and glucose responsiveness were significantly reduced by removal of the -310E-box from the HL promoter. Silencing of the USF1 gene by RNA interference reduced glucose responsiveness of the HL (-685/+13) promoter region by 50%. The hyperglycaemia in streptozotocin-treated rats was associated with similar increases in USF abundance in rat liver nuclei, but not with increased binding of USF to the rat Hl promoter region. CONCLUSIONS/
interpretationGlucose increases HL expression in HepG2 cells via elevation of USF1 and USF2. This mechanism may contribute to the development of the dyslipidaemia that is typical of type 2 diabetes.
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